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Protein Engineering by Yeast Surface Display
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Engineering of Yeast Glycoprotein Expression.

Charlot De Wachter1,2, Linde Van Landuyt1,2, Nico Callewaert3,4

  • 1VIB-UGent Center for Medical Biotechnology, Ghent, Belgium.

Advances in Biochemical Engineering/Biotechnology
|November 7, 2018
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Summary

Glyco-engineering yeast hosts improves recombinant protein production by modifying glycosylation. This overcomes immune responses and rapid clearance, making yeast suitable for biopharmaceutical manufacturing.

Keywords:
FungiN-glycosylation engineeringO-glycosylation engineeringPichia pastorisRecombinant protein expressionSaccharomyces cerevisiaeYeast

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Biopharmaceutical Manufacturing

Background:

  • Yeasts are efficient hosts for recombinant protein production due to rapid growth and cost-effective media.
  • A significant limitation is yeast-specific glycosylation, which differs from mammalian cells and can cause adverse effects on therapeutic proteins.
  • Glycosylation impacts protein folding, pharmacokinetics, and pharmacodynamics, and yeast's hypermannosylated structures can trigger immune responses.

Purpose of the Study:

  • To address the challenge of yeast-specific glycosylation in recombinant protein production.
  • To highlight advancements in glyco-engineering strategies for yeast hosts.
  • To enable yeast to regain its position in biopharmaceutical manufacturing.

Main Methods:

  • Glyco-engineering of N- and O-type glycosylation pathways in yeast.
  • Removal or reduction of yeast-specific glycans.
  • Introduction of humanized glycosylation pathways.

Main Results:

  • Development of effective solutions for modifying yeast glycosylation.
  • Overcoming challenges associated with yeast-specific glycan structures.
  • Enabling the production of therapeutic proteins with improved properties.

Conclusions:

  • Glyco-engineered yeasts offer a viable solution for producing safe and effective biopharmaceuticals.
  • These advancements are crucial for optimizing recombinant protein production in yeast.
  • Yeast hosts are poised to become leading platforms for biopharmaceutical manufacturing once again.